FGF3 FROM XENOPUS-LAEVIS

Fibroblast growth factor 3 (FGF3) was first identified as the product of a cellular oncogene activated by mouse mammary tumour virus but its normal role appears to be in the developing embryo. To gain further i nsights into its function, we have isolated sequences encoding the FGF 3 homologue in Xenopus laevis, XFGF3. COS-1 cells transfected with XFG F3 cDNA express a 31 kDa product, p31, generated by signal peptide cle avage and Asn-linked glycosylation at the single consensus site. This product is secreted and becomes associated with the cell surface and e xtracellular matrix. Proteolytic cleavage of p31 in the extracellular compartment results in an amino-terminally truncated product, p27, tha t is also glycosylated. Both p31 and p27 bind quantitatively to hepari n-Sepharose and can be displaced from the cell surface and extracellul ar matrix by soluble heparin. Conditioned medium containing these two proteins is capable of inducing transient morphological transformation of NIH3T3 cells and of stimulating DNA synthesis in quiescent C57MG a nd BALB/MK cells which express different isoforms of FGF receptors 1 a nd 2. Since XFGF3 behaves very differently from its mouse counter-part , we constructed chimeras in which amino-terminal sequences from XFGF3 were fused with carboxy-terminal sequences from mouse FGF3. Increasin g the contribution from mouse FGF3 led to a more restricted host range for the chimeric ligand.